Li, T.Y., A.M. Brennan, N.M. Wedick, C. Mantzoros, N. Rifai, F.B. Hu, 2009. Regular Consumption of Nuts Is Associated with a Lower Risk of Cardiovascular Disease in Women with Type 2 Diabetes. J. Nutr.139:1333-1338.
Higher nut consumption has been associated with lower risk of coronary heart disease (CHD) events in several epidemiologic studies. The study examined the association between intake of nuts and incident cardiovascular disease (CVD) in a cohort of women with type 2 diabetes. For the primary analysis, there were 6309 women with type 2 diabetes who completed a validated FFQ every 2-4 y between 1980 and 2002 and were without CVD or cancer at study entry. Major CVD events included incident myocardial infarction (MI), revascularization, and stroke. During 54,656 person-years of follow-up, there were 452 CHD events (including MI and revascularization) and 182 incident stroke cases. Frequent nut and peanut butter consumption was inversely associated with total CVD risk in age-adjusted analyses. After adjustment for conventional CVD risk factors, consumption of at least 5 servings/wk of nuts or peanut butter [serving size, 28 g (1 ounce) for nuts and 16 g (1 tablespoon) for peanut butter] was significantly associated with a lower risk of CVD (relative risk = 0.56; 95% CI: 0.36-0.89). Furthermore, when we evaluated plasma lipid and inflammatory biomarkers, we observed that increasing nut consumption was significantly associated with a more favorable plasma lipid profile, including lower LDL cholesterol, non-HDL cholesterol, total cholesterol, and apolipoprotein-B-100 concentrations. However, we did not observe significant associations for HDL cholesterol or inflammatory markers. These data suggest that frequent nut and peanut butter consumption is associated with a significantly lower CVD risk in women with type 2 diabetes.
Velliquette, R.A., P.J. Gillies, P.M. Kris-Etherton, J.W. Green, G. Zhao, J.P. Vanden Heuvel, 2009. Regulation of human stearoyl-CoA desaturase by omega-3 and omega-6 fatty acids: Implications for the dietary management of elevated serum triglycerides. Journal of Clinical Lipidology. 3:281-288.
Background: Polyunsaturated fatty acids lower serum triglycerides by a mechanism that may involve the inhibition of stearoyl-CoA desaturase (SCD). Objective: We sought to evaluate the effects of serum fatty acids on 1) the SCD index in a controlled clinical setting, and 2) SCD regulation in Hep G2 cells. Methods: The SCD index was determined in 23 subjects randomly sequenced through 3 diets for 6 weeks in a crossover study. Diets were variably enriched with n-3 and n-6 polyunsaturated fatty acids; notably, monounsaturated fatty acids were held constant. Effects of linoleic acid (LA), α-linolenic acid (ALA), and eicosapentaenoic acid (EPA) on mRNA levels of SCD, fatty acid elongases 5 and 6 (Elovl5 and Elovl6), fatty acid synthase, carnitine palmitoyltransferase-1, and sterol response element binding protein-1c were investigated in Hep G2 cells after 24-hour incubations. Results: The SCD indexes C18:1/18:0 and C16:1/C16:0 were significantly (P < .0001) correlated with serum TG with R2 values of 0.71 and 0.58. The correlation was negatively associated with LA and positively associated with ALA. LA and EPA decreased SCD mRNA (EC50 of 0.50 and 1.67 µM), whereas ALA did not. Likewise, LA and EPA decreased sterol response element binding protein-1c mRNA (EC50 of 0.78 and 1.78 µM), but ALA did not. Similar results were observed for Elovl6. GW9662, a peroxisome proliferation activator receptor antagonist, did not obviate the effects of LA and EPA on SCD mRNA. Conclusions: Diets enriched in LA, ALA, and by metabolic inference EPA, can regulate SCD activity at the level of transcription, a nutritional intervention that may be useful in the management of increased levels of serum triglycerides in cardiometabolic disorders.
Rajaram, S., E.H. Haddad, A. Mejia, J. Sabate’, 2009. Walnuts and fatty fish influence different serum lipid fractions in normal to mildly hyperlipidemic individuals: a randomized controlled study. Am J Clin Nutr. 89(suppl):1657S-1663S.
Background: Increased consumption of n-3 (omega-3) fatty acids decreases the incidence of coronary heart disease (CHD). Objective: The objective was to determine whether walnuts (plant n-3 fatty acid) and fatty fish (marine n-3 fatty acid) have similar effects on serum lipid markers at intakes recommended for primary prevention of CHD. Design: In a randomized crossover feeding trial, 25 normal to mildly hyperlipidemic adults consumed 3 isoenergetic diets (’30% total fat and,10% saturated fat) for 4 wk each: a control diet (no nuts or fish), a walnut diet (42.5 g walnuts/10.1 mJ), or a fish diet (113 g salmon, twice/wk). Fasting blood was drawn at baseline and at the end of each diet period and analyzed for serum lipids. Results: Serum total cholesterol and LDL cholesterol concentrations in adults who followed the walnut diet (4.87 ± 0.18 and 2.77 ± 0.15 mmol/L, respectively) were lower than in those who followed the control diet (5.14 ± 0.18 and 3.06 ± 0.15 mmol/L, respectively) and those who followed the fish diet (5.33 ± 0.18 and 3.2 ± 0.15 mmol/L, respectively; P<0.0001). The fish diet resulted in decreased serum triglyceride and increased HDL-cholesterol concentrations (1.0 ± 0.11 and 1.23 ± 0.05 mmol/L, respectively) compared with the control diet (1.12 ± 0.11 and 1.19 ± 0.05 mmol/L, respectively) and the walnut diet (1.11 ± 0.11 mmol/L, P<0.05, and 1.18 ± 0.05 mmol/L, P<0.001, respectively). The ratios of total cholesterol: HDL cholesterol, LDL cholesterol:HDL cholesterol, and apolipoprotein B:apolipoprotein A-I were lower (P<0.05) in those who followed the walnut diet compared with those who followed the control and fish diets. Conclusions: Including walnuts and fatty fish in a healthy diet lowered serum cholesterol and triglyceride concentrations, respectively, which affects CHD risk favorably.
Banel, D.K., F.B. Hu, 2009. Effects of walnut consumption on blood lipids and other cardiovascular risk factors: a meta-analysis and systematic review. Am J Clin Nutr 90:1-8.
Background: Consumption of nuts has been associated with a decreased risk of cardiovascular disease events and death. Walnuts in particular have a unique profile: they are rich in polyunsaturated fatty acids, which may improve blood lipids and other cardiovascular disease risk factors. Objectives: We aimed to conduct a literature review and a meta-analysis to combine the results from several trials and to estimate the effect of walnuts on blood lipids. Design: Literature databases were searched for published trials that compared a specifically walnut-enhanced diet with a control diet. We conducted a random-effects meta-analysis of weighted mean differences (WMDs) of lipid outcomes. Results: Thirteen studies representing 365 participants were included in the analysis. Diets lasted 4–24 wk with walnuts providing 10–24% of total calories. When compared with control diets, diets supplemented with walnuts resulted in a significantly greater decrease in total cholesterol and in LDL-cholesterol concentrations (total cholesterol: WMD = 210.3 mg/dL, P < 0.001; LDL cholesterol: WMD = 29.2 mg/dL, P < 0.001). High-density lipoprotein (HDL) cholesterol and triglycerides were not significantly affected by walnut diets more than with control diets (HDL cholesterol: WMD = 20.2, P = 0.8; triglycerides: WMD = 23.9, P = 0.3). Other results reported in the trials indicated that walnuts provided significant benefits for certain antioxidant capacity and inflammatory markers and had no adverse effects on body weight [body mass index (kg/m2): WMD = 20.4, P = 0.5; weight (kg): WMD = 20.05, P = 0.97]. Conclusions: Overall, high-walnut-enriched diets significantly decreased total and LDL cholesterol for the duration of the short-term trials. Larger and longer-term trials are needed to address the effects of walnut consumption on cardiovascular risk and body weight.
Ros, E., 2009. Nuts and novel biomarkers of cardiovascular disease. Am J Clin Nutr. 89(suppl):1649S-56S.
Nuts are energy-dense foods, rich in total fat and unsaturated fatty acids. The favorable fatty acid profile probably contributes to the beneficial effects of nut consumption observed in epidemiologic studies (prevention of coronary heart disease and diabetes) and feeding trials (cholesterol lowering). Besides fat, the complex matrices of nuts contain many bioactive compounds: vegetable protein, fiber, minerals, tocopherols, and phenolic compounds. By virtue of their unique composition, nuts are likely to benefit newer cardiovascular risk biomarkers, such as LDL oxidizability, soluble inflammatory molecules, and endothelial dysfunction. Protection of LDL oxidation by nut intake has been documented in some, but not all, clinical studies. In one study, feeding one daily serving of mixed nuts was associated with lower oxidized LDL concentrations. Regarding inflammation, cross-sectional studies have shown that nut consumption is associated with lower concentrations of circulating inflammatory molecules and higher plasma adiponectin, a potent anti-inflammatory adipokine. Clinical studies with nuts have documented reduced inflammatory cytokine concentrations but no consistent changes of C-reactive protein. Only walnuts have been formally tested for effects on endothelial function. After both walnut diets and single walnut meals, favorable vasoreactivity changes have been observed. Walnut consumption also reduced expression of endothelin 1, a potent endothelial activator, in an animal model of accelerated atherosclerosis. Beneficial effects on vascular reactivity may be ascribed to several constituents of walnuts: L-arginine, the precursor of nitricoxide, a-linolenic acid, and phenolic antioxidants. Although more studies are warranted, the emerging picture is that nut consumption beneficially influences cardiovascular risk beyond cholesterol lowering.
Rajaram S, Connell KM, Sabaté J., 2009. Effect of almond-enriched high-monounsaturated fat diet on selected markers of inflammation: a randomized, controlled, crossover study. Br J Nutr. Oct 29:1-6. [Epub ahead of print]
Frequent consumption of nuts lowers the risk of coronary heart disease (CHD). While lowering blood lipids is one of the mechanisms for cardio-protection, this study sought to determine if monounsaturated fat rich almonds also influences other CHD risk factors such as inflammation and hemostasis. This was a randomized, controlled, crossover feeding study with 25 healthy adults (11 men; 14 women), age 22-53 y. Following a 2 week run-in phase (34% energy from fat), subjects were assigned in random order to 3 diets for 4 weeks each: a heart healthy control diet with no nuts (<30% energy from fat), low almond diet and high almond diet (10% or 20% isoenergetic replacement of control diet with almonds respectively). Serum E-selectin was significantly lower on the high almond diet compared to the control diet. E-selectin decreased as the percentage of energy from almonds increased (P <0.0001). C-reactive protein (CRP) was lower in both the almond diets compared to the control diet. A clear dose response was not observed for either E-selectin or CRP. There was no effect of diet on interleukin-6 or fibrinogen. Tissue plasminogen activator antigen was significantly lower on the control and high almond diets compared to the low almond diet, although the values were within normal range. In conclusion, consumption of almonds influenced a few but not all of the markers of inflammation and hemostasis. A clear dose response was not observed for any of the markers studied.
Lopez-Uriarte. P., M. Bullo, P. Casas-Agustench, N. Babio, J. Salas-Salvado, 2009. Nuts and oxidation: a systematic review. Nutrition Reviews. 67(9):497-508.
In recent years, nuts have received special attention because of their potential role in preventing cardiovascular disease. Because nuts are very rich in total fat that can potentially be oxidized and their skins contain several antioxidants, studies have been conducted to evaluate the potential effect of nut consumption on oxidative stress. This review evaluates the in vitro and in vivo studies conducted in animals or humans to analyze the effect of nuts on oxidation.
Escurriol, V., Cofán, M., M. Serra, M. Bullo’, J. Basora, J. Salas-Salvado’, D. Corella, I. Zazpe, M.A. Martínez-González, V. Ruiz-Gutiérrez , R. Estruch, E. Ros, 2009. Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet. Eur J Nutr. 48(6):373-382.
Background: Phytosterols in natural foods are thought to inhibit cholesterol absorption. The Mediterranean diet is rich in phytosterol-containing plant foods. Aim of the study: To assess whether increasing phytosterols intake from natural foods was associated with a cholesterol-lowering effect in a substudy of a randomized trial of nutritional intervention with Mediterranean diets for primary cardiovascular prevention (PREDIMED study). Methods: One hundred and six high cardiovascular risk subjects assigned to two Mediterranean diets supplemented with virgin olive oil (VOO) or nuts, which are phytosterols-rich foods, or advice on a low-fat diet. Outcomes were 1-year changes in nutrient intake and serum levels of lipids and non-cholesterol sterols. Results: Average phytosterol intake increased by 76, 158 and 15 mg/day in participants assigned VOO, nuts and low-fat diets, respectively. Compared to participants in the low-fat diet group, changes in outcome variables were observed only in those in the Mediterranean diet with nuts group, with increases in intake of fiber, polyunsaturated fatty acids and phytosterols (P<0.020, all) and significant (P<0.05) reductions of LDL-cholesterol (0.27 mmol/l or 8.3%) and the LDL/HDL-cholesterol ratio (0.29 mmol/l or 11.5%). Variations in saturated fat, cholesterol or fiber intake were unrelated to LDL-cholesterol changes. In the whole group, changes in serum sitosterol-to-cholesterol, which reflect those of dietary phytosterol intake and absorption, correlated inversely to LDL-cholesterol changes (r = -0.256; P = 0.008). In multivariate analyses, baseline LDL-cholesterol, increases in serum sitosterol ratios and statin use were independently associated with LDL-cholesterol reductions. Conclusions: Small amounts of phytosterols in natural foods appear to be bioactive in cholesterol lowering.
Papoutsi, Z., E. Kassi, I. Chinou, M. Halabalaki, L.A. Skaltsounis, P. Moutsatsou, 2008. Walnut extract (Juglans regia L.) and its component ellagic acid exhibit anti-inflammatory activity in human aorta endothelial cells and osteoblastic activity in the cell line KS483. British Journal of Nutrition. 99(4):715-22.
Epidemiological studies suggest that the incidence of CVD and postmenopausal osteoporosis is low in the Mediterranean area, where herbs and nuts, among others, play an important role in nutrition. In the present study, we sought a role of walnuts (Juglans regia L.) in endothelial and bone-cell function. As the endothelial cell expression of adhesion molecules has been recognised as an early step in inflammation and atherogenesis, we examined the effect of walnut methanolic extract and ellagic acid, one of its major polyphenolic components (as shown by HPLC analysis), on the expression of vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1 in human aortic endothelial cells. After incubating the cells with TNF-α (1 ng/ml) in the absence and in the presence of walnut extract (10–200 µg/ml) or ellagic acid (10-7–10-5 M), the VCAM-1 and ICAM-1 expression was quantified by cell-ELISA. We further evaluated the effect of walnut extract (10–50 mg/ml), in comparison with ellagic acid (10-9–10-6 M), on nodule formation in the osteoblastic cell line KS483.Walnut extract and ellagic acid decreased significantly the TNF-a-induced endothelial expression of both VCAM-1 and ICAM-1 (P < 0.01; P < 0.001). Both walnut extract (at 10–25µg/ml) and ellagic acid (at 10-9–10-8 M) induced nodule formation in KS483 osteoblasts. The present results suggest that the walnut extract has a high anti-atherogenic potential and a remarkable osteoblastic activity, an effect mediated, at least in part, by its major component ellagic acid. Such findings implicate the beneficial effect of a walnut-enriched diet on cardioprotection and bone loss.
Zazpe, I.A. Sanchez-Tainta, R. Estruch, R.M. Lamuela-Raventos, H. Schröder, J. Salas-Salvado, D. Corella, M. Fiol, E. Gomez-Gracia, F. Aros, E. Ros, V. Ruíz-Gutierrez, P. Iglesias, M. Conde-Herrera, M.A. Martinez-Gonzalez, 2008. A large randomized individual and group intervention conducted by registered dietitians increased adherence to Mediterranean-type diets: the PREDIMED study. J Am Diet Assoc. 108:7 1134-1143.
Objective: To assess the effectiveness of an intervention aimed to increase adherence to a Mediterranean diet. Design: A 12-month assessment of a randomized primary prevention trial. Subjects/settings: One thousand five hundred fifty-one asymptomatic persons aged 55 to 80 years, with diabetes or ≥3 cardiovascular risk factors. Intervention: Participants were randomly assigned to a control group or two Mediterranean diet groups. Those allocated to the two Mediterranean diet groups received individual motivational interviews every 3 months to negotiate nutrition goals, and group educational sessions on a quarterly basis. One Mediterranean diet group received free virgin olive oil (1L/week), the other received free mixed nuts (30 g/day). Participants in the control group received verbal instructions and a leaflet recommending the National Cholesterol Education Program Adult Treatment Panel III dietary guidelines. Main outcome measures: Changes in food and nutrient intake after 12 months. Statistical analyses: Paired t tests (for within-group changes) and analysis of variance (for between-group changes) were conducted. Results: Participants allocated to both Mediterranean diets increased their intake of virgin olive oil, nuts, vegetables, legumes, and fruits (P<0.05 for all within- and between-group differences). Participants in all three groups decreased their intake of meat and pastries, cakes, and sweets (P<0.05 for all). Fiber, monounsaturated fatty acid, and polyunsaturated fatty acid intake increased in the Mediterranean diet groups (P<0.005 for all). Favorable, although nonsignificant, changes in intake of other nutrients occurred only in the Mediterranean diet groups. Conclusions: A 12-month behavioral intervention promoting the Mediterranean diet can favorably modify an individual’s overall food pattern. The individual motivational interventions together with the group sessions and the free provision of high-fat and palatable key foods customary to the Mediterranean diet were effective in improving the dietary habits of participants in this trial.
